ASN Kidney Week 2019
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Hypothermic Oxygenated Perfusion Versus Static Cold Storage For
JMIR RESEARCH PROTOCOLS Ravaioli et al Protocol Hypothermic Oxygenated Perfusion Versus Static Cold Storage for Expanded Criteria Donors in Liver and Kidney Transplantation: Protocol for a Single-Center Randomized Controlled Trial Matteo Ravaioli1, MD, PhD, Prof Dr; Lorenzo Maroni1, MD; Andrea Angeletti2, MD; Guido Fallani1, MD; Vanessa De Pace1, MS; Giuliana Germinario1, MS; Federica Odaldi1, MD; Valeria Corradetti2, MD; Paolo Caraceni1, MD, Prof Dr; Maurizio Baldassarre1, MS, PhD; Francesco Vasuri3, MD, PhD; Antonia D©Errico3, MD, Prof Dr; Gabriela Sangiorgi4, MD; Antonio Siniscalchi1, MD; Maria Cristina Morelli1, MD; Anna Rossetto1, MD; Vito Marco Ranieri1, Prof Dr; Matteo Cescon1, MD, PhD, Prof Dr; Massimo Del Gaudio1, MD, PhD; Chiara Zanfi1, MD; Valentina Bertuzzo1, MD, PhD; Giorgia Comai2, MD, PhD; Gaetano La Manna2, MD, PhD, Prof Dr 1Department of Medical and Surgical Sciences, University of Bologna Sant©Orsola-Malpighi Hospital, Bologna, Italy 2Department of Experimental Diagnostic and Specialty Medicine, University of Bologna Sant©Orsola-Malpighi Hospital, Bologna, Italy 3Pathology Division, University of Bologna Sant©Orsola-Malpighi Hospital, Bologna, Italy 4Emilia-Romagna Transplantation Referral Center, Emilia-Romagna, Italy Corresponding Author: Matteo Ravaioli, MD, PhD, Prof Dr Department of Medical and Surgical Sciences University of Bologna Sant©Orsola-Malpighi Hospital Via Massarenti, 9 Bologna, 40138 Italy Phone: 39 051 2144810 Email: [email protected] Abstract Background: Extended criteria donors (ECD) are widely utilized due to organ shortage, but they may increase the risk of graft dysfunction and poorer outcomes. Hypothermic oxygenated perfusion (HOPE) is a recent organ preservation strategy for marginal kidney and liver grafts, allowing a redirect from anaerobic metabolism to aerobic metabolism under hypothermic conditions and protecting grafts from oxidative species±related damage. -
Endothelin System and Therapeutic Application of Endothelin Receptor
xperim ACCESS Freely available online & E en OPEN l ta a l ic P in h l a C r m f o a c l a o n l o r g u y o J Journal of ISSN: 2161-1459 Clinical & Experimental Pharmacology Research Article Endothelin System and Therapeutic Application of Endothelin Receptor Antagonists Abebe Basazn Mekuria, Zemene Demelash Kifle*, Mohammedbrhan Abdelwuhab Department of Pharmacology, School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia ABSTRACT Endothelin is a 21 amino acid molecule endogenous potent vasoconstrictor peptide. Endothelin is synthesized in vascular endothelial and smooth muscle cells, as well as in neural, renal, pulmonic, and inflammatory cells. It acts through a seven transmembrane endothelin receptor A (ETA) and endothelin receptor B (ETB) receptors belongs to G protein-coupled rhodopsin-type receptor superfamily. This peptide involved in pathogenesis of cardiovascular disorder like (heart failure, arterial hypertension, myocardial infraction and atherosclerosis), renal failure, pulmonary arterial hypertension and it also involved in pathogenesis of cancer. Potentially endothelin receptor antagonist helps the treatment of the above disorder. Currently, there are a lot of trails both per-clinical and clinical on endothelin antagonist for various cardiovascular, pulmonary and cancer disorder. Some are approved by FAD for the treatment. These agents are including both selective and non-selective endothelin receptor antagonist (ETA/B). Currently, Bosentan, Ambrisentan, and Macitentan approved -
Label-Free Proteomic Methodology for the Analysis of Human Kidney Stone Matrix Composition Frank A
Witzmann et al. Proteome Science (2016) 14:4 DOI 10.1186/s12953-016-0093-x METHODOLOGY Open Access Label-free proteomic methodology for the analysis of human kidney stone matrix composition Frank A. Witzmann1*, Andrew P. Evan2, Fredric L. Coe3, Elaine M. Worcester3, James E. Lingeman4 and James C. Williams Jr2 Abstract Background: Kidney stone matrix protein composition is an important yet poorly understood aspect of nephrolithiasis. We hypothesized that this proteome is considerably more complex than previous reports have indicated and that comprehensive proteomic profiling of the kidney stone matrix may demonstrate relevant constitutive differences between stones. We have analyzed the matrices of two unique human calcium oxalate stones (CaOx-Ia and CaOx-Id) using a simple but effective chaotropic reducing solution for extraction/solubilization combined with label-free quantitative mass spectrometry to generate a comprehensive profile of their proteomes, including physicochemical and bioinformatic analysis.` Results: We identified and quantified 1,059 unique protein database entries in the two human kidney stone samples, revealing a more complex proteome than previously reported. Protein composition reflects a common range of proteins related to immune response, inflammation, injury, and tissue repair, along with a more diverse set of proteins unique to each stone. Conclusion: The use of a simple chaotropic reducing solution and moderate sonication for extraction and solubilization of kidney stone powders combined with label-free quantitative mass spectrometry has yielded the most comprehensive list to date of the proteins that constitute the human kidney stone proteome. Keywords: Calcium oxalate, Kidney stone, Label-free quantitative liquid chromatography–tandem mass spectrometry, Matrix protein, Nephrolithiasis, Proteomics Background deposition is the primary event, at least in the formation The organic matrix within urinary stones has long been of CaOx stones over plaque. -
FY 2020 Results Conference Call and Webcast for Investors and Analysts
FY 2020 results Conference call and webcast for investors and analysts 11 February 2021 Forward-looking statements In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act of 1995, AstraZeneca (hereafter ‘the Group’) provides the following cautionary statement: this document contains certain forward-looking statements with respect to the operations, performance and financial condition of the Group, including, among other things, statements about expected revenues, margins, earnings per share or other financial or other measures. Although the Group believes its expectations are based on reasonable assumptions, any forward-looking statements, by their very nature, involve risks and uncertainties and may be influenced by factors that could cause actual outcomes and results to be materially different from those predicted. The forward-looking statements reflect knowledge and information available at the date of preparation of this document and the Group undertakes no obligation to update these forward-looking statements. The Group identifies the forward-looking statements by using the words 'anticipates', 'believes', 'expects', 'intends' and similar expressions in such statements. Important factors that could cause actual results to differ materially from those contained in forward-looking statements, certain of which are beyond the Group’s control, include, among other things: the risk of failure or delay in delivery of pipeline or launch of new medicines; the risk of failure -
Zibotentan, an Endothelin a Receptor Antagonist, Prevents Amyloid-Я
Journal of Alzheimer’s Disease 73 (2020) 1185–1199 1185 DOI 10.3233/JAD-190630 IOS Press Zibotentan, an Endothelin A Receptor Antagonist, Prevents Amyloid--Induced Hypertension and Maintains Cerebral Perfusion Jennifer C. Palmera,1, Hannah M. Taylera,1, Laurence Dyera, Patrick G. Kehoea, Julian F.R. Patonb and Seth Lovea,∗ aTranslational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK bDepartment of Physiology, Faculty of Medical & Health Sciences, University of Auckland, New Zealand Accepted 25 November 2019 Abstract. Cerebral blood flow is reduced in Alzheimer’s disease (AD), which is associated with mid-life hypertension. In people with increased cerebral vascular resistance due to vertebral artery or posterior communicating artery hypoplasia, there is evidence that hypertension develops as a protective mechanism to maintain cerebral perfusion. In AD, amyloid- (A) accumulation may similarly raise cerebral vascular resistance by upregulation of the cerebral endothelin system. The level of endothelin-1 in brain tissue correlates positively with A load and negatively with markers of cerebral hypoperfusion such as increased vascular endothelial growth factor. We previously showed that cerebroventricular infusion of A40 exacerbated pre- existing hypertension in Dahl rats. We have investigated the effects of 28-day cerebral infusion of A40 on blood pressure and heart rate and their variability; carotid flow; endothelin-1; and markers of cerebral oxygenation, in the (normotensive) Wistar rat, and the modulatory influence of the endothelin A receptor antagonist Zibotentan (ZD4054). Cerebral infusion of A caused progressive rise in blood pressure (p < 0.0001) (paired t-test: increase of 3 (0.1–5.6) mmHg (p = 0.040)), with evidence of reduced baroreflex responsiveness, and accumulation of A and elevated endothelin-1 in the vicinity of the infusion. -
Ischemia-Reperfusion Injuries Assessment During Pancreas Preservation
International Journal of Molecular Sciences Review Ischemia-Reperfusion Injuries Assessment during Pancreas Preservation Thomas Prudhomme 1,2 , John F. Mulvey 3 , Liam A. J. Young 3,4 , Benoit Mesnard 1,2 , Maria Letizia Lo Faro 3, Ann Etohan Ogbemudia 3, Fungai Dengu 3, Peter J. Friend 3, Rutger Ploeg 3, James P. Hunter 3 and Julien Branchereau 1,2,3,* 1 Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, 44000 Nantes, France; [email protected] (T.P.); [email protected] (B.M.) 2 Centre de Recherche en Transplantation et Immunologie (CRTI) UMR1064, INSERM, Université de Nantes, 44000 Nantes, France 3 Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK; [email protected] (J.F.M.); [email protected] (L.A.J.Y.); [email protected] (M.L.L.F.); [email protected] (A.E.O.); [email protected] (F.D.); [email protected] (P.J.F.); [email protected] (R.P.); [email protected] (J.P.H.) 4 Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK * Correspondence: [email protected] Abstract: Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. To date in pancreas transplantation, static cold storage (SCS) Citation: Prudhomme, T.; Mulvey, is the most widely practiced method of organ preservation. The first experiments in ex vivo perfusion J.F.; Young, L.A.J.; Mesnard, B.; Lo of the pancreas were performed at the beginning of the 20th century. -
Experimental Models of Prostate Cancer Bone Metastasis - Establishment, Characterization and Imaging of Xenograft Bone Metastasis Models
Experimental Models of Prostate Cancer Bone Metastasis - Establishment, characterization and imaging of xenograft bone metastasis models - PhD thesis presented by Marta Garcia López To obtain the degree of PhD for the Universitat Autònoma de Barcelona (UAB) PhD thesis done at the Research Unit in Biomedicine and Translational and Pediatrics Oncology, at the Vall d’Hebron Research Institute, Vall d’Hebron Hospital, under the supervision of Drs. Jaume Reventós i Puigjaner, Andreas Doll and Juan Morote Robles Doctoral study in Biochemistry, Molecular Biology and Biomedicine. Universitat Autònoma de Barcelona, Faculty of Bioscience, Department of Biochemistry and Molecular Biology Universitat Autònoma de Barcelona, 2013 Dr. Jaume Reventós Puigjaner Dr. Andreas Doll Dr. Juan Morote Robles Marta Garcia López No entiendes realmente algo a menos que seas capaz de explicárselo a tu abuela. Albert Einstein Summary In industrialized countries, prostate cancer (PCa) is the most common malignancy in men, but mortality rates are much lower than those recorded in developing countries, reflecting benefits from advances in early diagnosis and effective treatment. However, the metastatic disease rather than the primary tumour is responsible for much of the resulting morbidity and mortality. Skeletal metastases occur in more than 70% of cases of late-stage of PCa and they confer a high level of morbidity, a 5-year survival rate of 25% and median survival of approximately 40 months. Though fractures and spinal cord compression are potential complications, the most common symptom of bone metastases is pain. Bone metastases from PCa lead to an accelerated bone turnover state that features pathological activation of both osteoblasts and osteoclasts. -
Tanibirumab (CUI C3490677) Add to Cart
5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor -
Utilizing Animal Studies to Evaluate Organ Preservation Devices ______Guidance for Industry and Food and Drug Administration Staff
Contains Nonbinding Recommendations Utilizing Animal Studies to Evaluate Organ Preservation Devices ______________________________________________________________________________ Guidance for Industry and Food and Drug Administration Staff Document issued on May 8, 2019. The draft of this document was issued on September 15, 2017. For questions about this document, contact DHT3A: Division of Renal, Gastrointestinal, Obesity, and Transplant Devices at 301-796-7030. U.S. Department of Health and Human Services Food and Drug Administration Center for Devices and Radiological Health Contains Nonbinding Recommendations Preface Public Comment You may submit electronic comments and suggestions at any time for Agency consideration to https://www.regulations.gov. Submit written comments to the Dockets Management Staff, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852. Identify all comments with the docket number FDA-2017-D-4886. Comments may not be acted upon by the Agency until the document is next revised or updated. Additional Copies Additional copies are available from the Internet. You may also send an e-mail request to [email protected] to receive a copy of the guidance. Please use the document number 1500083 to identify the guidance you are requesting. Contains Nonbinding Recommendations Table of Contents I. Introduction ........................................................................................................................... 1 II. Scope .................................................................................................................................... -
Uromodulin Levels Associate with a Common UMOD Variant and Risk for Incident CKD
CLINICAL EPIDEMIOLOGY www.jasn.org Uromodulin Levels Associate with a Common UMOD Variant and Risk for Incident CKD ʈ ʈ Anna Ko¨ttgen,* Shih-Jen Hwang,†‡ Martin G. Larson,§ Jennifer E. Van Eyk, Qin Fu, Emelia J. Benjamin,†¶ Abbas Dehghan,** Nicole L. Glazer,†† W.H. Linda Kao,* ʈʈ Tamara B. Harris,‡‡ Vilmundur Gudnason,§§ Michael G. Shlipak,¶¶ Qiong Yang,§ Josef Coresh,* Daniel Levy,†‡ and Caroline S. Fox†‡*** *Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; †Framingham Heart Study, Framingham, Massachusetts; ‡Center for Population Studies, National Heart, Lung, and Blood Institute, and ‡‡Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland; Departments of §Biostatistics and ʈ ¶Epidemiology, Boston University School of Public Health, Boston, Massachusetts; Department of Medicine, Johns Hopkins University, Baltimore, Maryland; **Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands; ††Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, ʈʈ Washington; §§Icelandic Heart Association Research Institute, Kopavogur, Iceland; University of Iceland, Reykjavik, Iceland; ¶¶General Internal Medicine Division, San Francisco VA Medical Center, University of California, San Francisco, California; and ***Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts ABSTRACT Common variants in the region of the UMOD gene, which encodes uromodulin (Tamm-Horsfall protein), associate with chronic kidney disease (CKD) and estimated GFR (eGFR). Whether uromodulin levels associate with UMOD variants or with the risk for developing CKD is unknown. We conducted an age- and gender- matched case-control study (n ϭ 200) of incident CKD (eGFR Ͻ60 ml/min per 1.73 m2) within the Framingham Heart Study (FHS). -
Characterisation of Proendothelin-1 Derived Peptides and Evaluation of Their Utility As Biomarkers of Vascular and Renal Pathologies
Characterisation of Proendothelin-1 Derived Peptides and Evaluation of Their Utility as Biomarkers of Vascular and Renal Pathologies Jale Yuzugulen A thesis submitted for the degree of Doctor of Philosophy (Ph.D) in the Barts and the London School of Medicine and Dentistry of the Queen Mary, University of London 2014 Centre for Translational Medicine & Therapeutics, William Harvey Research Institute, John Vane Science Centre Charterhouse Square London UK i Statement of originality I, Jale Yuzugulen, confirm that the research included within this thesis is my own work or that where it has been carried out in collaboration with, or supported by others, that this is duly acknowledged below and my contribution indicated. Previously published material is also acknowledged below. I attest that I have exercised reasonable care to ensure that the work is original, and does not to the best of my knowledge break any UK law, infringe any third party’s copyright or other Intellectual Property Right, or contain any confidential material. I accept that the College has the right to use plagiarism detection software to check the electronic version of the thesis. I confirm that this thesis has not been previously submitted for the award of a degree by this or any other university. The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author. Signature: [ ] Date: 10/03/2014 ii List of publications and abstracts arising from this thesis: 1. Yuzugulen J, Wood EG, Douthwaite JA, Villar IC, Patel NS, Jegard J, Montoya A, Cutillas P, Hartley O, Ahluwalia A, Corder R. -
Mitochondrial Targeting Therapy Role in Liver Transplant Preservation Lines: Mechanism and Therapeutic Strategies
Open Access Review Article DOI: 10.7759/cureus.16599 Mitochondrial Targeting Therapy Role in Liver Transplant Preservation Lines: Mechanism and Therapeutic Strategies Anjli Tara 1, 2 , Jerry Lorren Dominic 3, 4, 5, 1 , Jaimin N. Patel 6 , Ishan Garg 7 , Jimin Yeon 7 , Marrium S. Memon 8 , Sanjay Rao Gergal Gopalkrishna Rao 9 , Seif Bugazia 10 , Tamil Poonkuil Mozhi Dhandapani 11, 12 , Amudhan Kannan 13, 14 , Ketan Kantamaneni 15, 16 , Myat Win 17, 1 , Terry R. Went 15 , Vijaya Lakshmi Yanamala 15 , Jihan A. Mostafa 18 1. General Surgery, California Institute of Behavioral Neurosciences & Psychology (CIBNP), Fairfield, USA 2. General Surgery, Liaquat University of Medical and Health Sciences (LUMHS), Jamshoro, PAK 3. General Surgery, Vinayaka Mission's Kirupananda Variyar Medical College, Salem, IND 4. General Surgery, Stony Brook Southampton Hospital, New York, USA 5. General Surgery and Orthopaedic Surgery, Cornerstone Regional Hospital, Edinburg, USA 6. Family Medicine, California Institute of Behavioral Neurosciences & Psychology (CIBNP), Fairfield, USA 7. Medicine, California Institute of Behavioral Neurosciences & Psychology (CIBNP), Fairfield, USA 8. Research, California Institute of Behavioral Neurosciences & Psychology (CIBNP), Fairfield, USA 9. Internal Medicine, California Institute of Behavioral Neurosciences & Psychology (CIBNP), Fairfield, USA 10. Faculty of Medicine, California Institute of Behavioral Neurosciences & Psychology (CIBNP), Fairfield, USA 11. Internal Medicine/Family Medicine, California Institute of Behavioral Neuroscience & Pyshology (CIBNP), Fairfield, USA 12. Internal Medicine, Medical City Plano, Plano, USA 13. Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, IND 14. General Surgery Research, California Institute of Behavioral Neurosciences & Psychology (CIBNP), Fairfield, USA 15. Surgery, California Institute of Behavioral Neurosciences & Psychology (CIBNP), Fairfield, USA 16.